The goal of this exploratory developmental project is to better understand the degree to which use of +/- 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and cannabis during late adolescence affect brain functioning. Marijuana and MDMA are used relatively widely in the United States and Western Europe with rates increasing particularly for adolescents. Animal models have suggested adverse brain changes associated with MDMA use. Although some human studies have shown neurocognitive deficits among MDMA users, these reports have been challenged by inadequately matched comparison groups, particularly with regards to other substance use, and recent substance use. Additionally, it is unknown how use of these substances during adolescent neuromaturational processes affect brain functioning and thinking abilities. Since most users of MDMA take other substances as well, a drug-using comparison group appears appropriate. The current proposal compares brain functioning using functional magnetic resonance imaging (fMRI) and neuropsychological (NP) performance between 3 groups of 16 to 18 year old adolescents: 1) users of MDMA and marijuana, 2) users of marijuana only, and 3) nonusers. Youth will be recruited from local high schools (N=9000) during twice-annual school-wide surveys conducted as part of another ongoing research project. Testing will take place after >28 days of abstinence from MDMA, cannabis, and other substance, confirmed by frequent toxicology screening in the four weeks before assessment. Results from this study will also be compared to those of alcohol use disordered adolescents in our current fMRI and NP studies. Based on animal models and existing data in humans, it is hypothesized that the MDMA+marijuana group will show a greater degree of abnormality on these measures than the marijuana only group or the non-using control group. We predict that cognitive performances related to serotonergic functioning, such as memory and impulsivity, will be particularly abnormal, with corresponding fMRI response decreases in prefrontal, orbitofrontal, and medial temporal cortices during tasks requiring these areas. A secondary aim of this project is to refine assessment methods by developing procedures for establishing 28 days of sobriety in youth and validating measures of intoxication and post-intoxication effects to help ascertain the pharmacology of drugs taken by teens.